COVID-19
Conditions
Keywords
ARDS, COVID 19, Bronchipret
Brief summary
There is currently an urgent need for effective and safe treatments of Coronavirus Disease (COVID) - 19 and the cytokine storm that is responsible for the development of patient's Acute Respiratory Distress Syndrome (ARDS). As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study is conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.
Detailed description
Although intensive research efforts have been underway worldwide, so far, only few effective treatment against the disease has been brought to the market in Germany. Based on the pathological features and different clinical phases of COVID-19, particularly in patients with moderate to severe COVID- 19, the classes of drugs used are antiviral agents (e.g., remdesivir), inflammation inhibitors/antirheumatic drugs (e.g., dexamethasone), low molecular weight heparins, plasma, and hyperimmune immunoglobulins Bronchipret exhibits multidirectional anti-inflammatory effects as demonstrated in vitro and in vivo studies. Several clinical trials have demonstrated positive effects of Bronchipret, a fixed combination of thyme herb and ivy leaf fluid extracts, on symptom relieve and recovery time in patients with acute bronchitis and cough. There is currently an urgent need for effective and safe treatments of COVID- 19 and the cytokine storm that is responsible for the development of Acute Respiratory Distress Syndrome (ARDS). As Bronchipret has been proven to be a very safe medicine, it is not expected that it would lead to the development of severe adverse effects in COVID-19 patients. Bronchipret can therefore be recommended as effective and safe supplementary treatments of COVID-19, even more so considering the positive effects shown in vitro. Thus, this randomized study will be conducted to assess the effect of Bronchipret on the immune response and recovery in patients with mild COVID-19 by assessing several blood parameters as well as the symptom recovery and improvement in comparison to patients who do not receive Bronchipret. Another aim of this feasibility study is to determine the best possible primary endpoint, i.e. which shows the greatest effect according to Cohen.
Interventions
DRUGBronchipret
Bronchipret syrup (3x 5,4 ml daily) until day 14
Sponsors
Bionorica SE
Dr. Frank Behrens
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
open-label
Intervention model description
Comparison of Verum (Bronchipret) versus no verum i.d. standard of care
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years and ≤ 75 years o If \> 50 years, complete COVID-19 vaccination mandatory 2. SARS-CoV-2 infection confirmed by PCR test ≤ 4 days before screening/baseline visit 3. Onset of the earliest symptoms \< 7 days before screening/baseline visit 4. Mild COVID-19 with the following symptoms (outpatient management/non hospitalized patients): ᴑ Cough and ᴑ At least one other symptom (e.g., sore throat, nasal congestion, headache, nausea, low energy/fatigue, muscle or body ache, shortness of breath, fever, diarrhea, altered sense of smell or taste) 5. Written informed consent obtained prior to the initiation of any protocol-required procedures by the patient 6. Willingness to comply to study procedures and study protocol
Exclusion criteria
1. WHO score ≥ 3 2. Other advanced or chronic lung diseases (Chronic obstructive pulmonary disease (COPD), silicosis, bronchial asthma) 3. Unable to take oral medication 4. Body mass index (BMI) \> 35 or ≤ 43kg 5. Requirement for oxygen administration 6. Current hospitalization 7. Known hypersensitivity to the active substances ivy, thyme, plants of the aralia family or other labiates (Lamiaceae), birch, mugwort, celery or to any of the excipients 8. Patients with rare hereditary fructose intolerance 9. Inability to monitor body temperature 10. Patients regularly taking immune suppressive medication, nonsteroidal anti-rheumatic drug(s) (NSARs) or steroids (e.g., because of underlying disease) 11. Known significant concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and with the study outcome such as stem cell or organ transplantation within the last 5 years, cardiovascular disease, diabetes mellitus, chronic liver disease, chronic kidney disease including dialysis patients, sickle cell anemia or thalassemia, and other forms of immunosuppression (e.g. tumor patients, HIV-infected patients with weakened immune system, iatrogenic immunosuppression) as judged by the study physician according to patient's reports. 12. COVID-19 vaccination planned within study period and/or COVID-19 vaccination within the last 28 days 13. Women pregnant (patient reported at pre-Screening and confirmation via pregnancy test at Screening/baseline) or nursing 14. Males or females of reproductive potential not willing to use effective contraception (defined as PEARL index \<1 - e.g. contraceptive pills/intra-uterine devices (IUD)) 15. Alcohol, drug or chemical abuse 16. Current participation in another interventional clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in average concentration of immunologic markers | Comparison Baseline to day 7 | concentration of Interleukin 2 (IL-2) |
| Change in average concentration of immunologic markers - IL4 | Comparison Baseline to day 7 | concentration of Interleukin (IL) 4 |
| Change in average concentration of immunologic markers - Interleukin (IL)-6 | Comparison Baseline to day 7 | concentration of IL-6 |
| Change in average concentration of immunologic markers - IL-8 | Comparison Baseline to day 7 | concentration of IL-8 |
| Change in average concentration of immunologic markers - IL-10 | Comparison Baseline to day 7 | concentration of IL-10 |
| Change in average concentration of immunologic markers - Interferon y | Comparison Baseline to day 7 | concentration of interferon (INF) y |
| Change in average concentration of immunologic markers- c-reactive protein (CRP) | Comparison Baseline to day 7 | concentration of c-reactive protein (CRP) |
| Change in average concentration of immunologic markers - IL-1β | Comparison Baseline to day 7 | concentration of IL-1β |
| Change in average concentration of immunologic markers - Interferon (INF) α | Comparison Baseline to day 7 | concentration of INFα |
| Change in average concentration of immunologic markers - TNFα | Comparison Baseline to day 7 | concentration of tumor necrosis factor alpha (TNFα) |
| Change in average number of immunologic markers - neutrophils | Comparison Baseline to day 7 | number of neutrophils |
| Change in average number of immunologic markers - lymphocytes | Comparison Baseline to day 7 | number of lymphocytes |
| Change in average number of immunologic markers - monocytes | Comparison Baseline to day 7 | number of monocytes |
| Change in average number of immunologic markers - eosinophils | Comparison Baseline to day 7 | number of eosinophils |
| Change in average number of immunologic markers - basophils | Comparison Baseline to day 7 | number of basophils |
| Change in average number of immunologic markers - platelets | Comparison Baseline to day 7 | number of platelets |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of blood parameters and change to BL (percentage): IL10 | Day 7 | percentage of change of concentration of IL-10 |
| Concentration of blood parameters and change to BL (INFy percentage): | Day 4 | percentage of change of concentration of INFy |
| Concentration of blood parameters and change to BL (absolute change INFy): | Day 4 | absolute change of concentration of INFy |
| Concentration of blood parameters and change to BL (percentage): INFy | Day 7 | percentage of change of concentration of INFy |
| Concentration of blood parameters and change to BL (absolute change): INFy | Day 7 | absolute change of concentration of INFy |
| Concentration of blood parameters and change to BL (absolute change): CRP | Day 4 | absolute change of concentration of CRP |
| Concentration of blood parameters and change to BL (percentage): CRP | Day 4 | percentage of change of concentration of CRP |
| Concentration of blood parameters and change to BL (percentage): IL-1β | Day 4 | percentage of change of concentration of IL-1β |
| Concentration of blood parameters and change to BL (absolute change): IL-1β | Day 4 | absolute change of concentration of IL-1β |
| Concentration of blood parameters and change to BL (absolute change): INFα | Day 4 | absolute change of concentration of INFα |
| Concentration of blood parameters and change to BL (percentage): INFα | Day 4 | percentage of change of concentration of INFα |
| Concentration of blood parameters and change to BL (absolute change):INFα | Day 7 | absolute change of concentration of INFα |
| Concentration of blood parameters and change to BL (absolute change): TNFα, | Day 4 | absolute change of concentration of TNFα, |
| Concentration of blood parameters and change to BL (percentage): TNFα, | Day 4 | percentage of change of concentration of TNFα, |
| Concentration of blood parameters and change to BL (percentage): neutrophils | Day 4 | percentage change of neutrophils |
| Concentration of blood parameters and change to BL (absolute change): neutrophils | Day 4 | absolute change of neutrophils number |
| Concentration of blood parameters and change to BL (absolute change): lymphocytes | Day 4 | absolute change of lymphocytes number |
| Concentration of blood parameters and change to BL (percentage): lymphocytes | Day 4 | percentage change of lymphocytes |
| Concentration of blood parameters and change to BL (percentage): monocytes | Day 4 | percentage change of monocytes |
| Concentration of blood parameters and change to BL (absolute change): monocytes | Day 4 | absolute change of monocytes number |
| Concentration of blood parameters and change to BL (absolute change): eosinophils | Day 4 | absolute change of eosinophils number |
| Concentration of blood parameters and change to BL (percentage): eosinophils | Day 4 | percentage of change of eosinophils |
| Neutrophil to lymphocyte ratio | Day 4 | Neutrophil to lymphocyte number ratio |
| IL-6/IL-10 ratio | Day 4 | IL-6/IL-10 concentration ratio |
| IL-6/INFy ratio | Day 14 | IL-6/INFy concentration ratio |
| Assessment of symptom improvement/worsening | Day 4 | FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14) |
| Assessment of number of symptoms | Day 4 | FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14) |
| Assessment of symptom distribution | Day 4 | FDA (Federal drug agency) recommended symptom questionnaire - higher scores describe worse symptoms, scoring 0 to 3 (question 1 to 12) and 0 to 2 (question 13 and 14) |
| Assessment of defervescence | Day 28 | Time to defervescence in days |
| Assessment of defervescence - number of patients | Day 28 | Number of patients who achieved defervescence |
| Assessment of defervescence - portion of patients | Day 28 | Proportion of patients who achieved defervescence |
| Assessment of improvement or absence of coughing | Day 28 | Time to cough reported as mild oder non existent in days |
| Assessment of improvement or absence of coughing - proportion of patients | Day 28 | proportion of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent |
| Assessment of improvement or absence of coughing - number of patients | Day 28 | Number of patients with moderate or severe cough at BL who achieved cough reported as mild or none existent |
| Assessment of intensity and distribution of most bothersome symptom | Day 28 | Intensity of most bothersome symptom assessment done by visual analogue scale (VAS) and change to Baseline - score 0 to 10 cm, higher values describe higher intensity |
| Proportion of patients who return to usual health | Day 28 | proportion of patients who return to usual health |
| Number of patients who return to usual health | Day 28 | Number of patients who return to usual health |
| proportion of patients who return to usual activity | Day 28 | proportion of patients who return to usual activity |
| Requirement of hospitalisation or oxygen supplementation | Day 28 | Number of patients requiring hospitalisation or oxygen supplementation (patient reported) |
| Disease progression/improvement | Day 4 | Number of patients with improved or progressed disease state (according to world health organisation (WHO) scale) - Score 0 - 10, higher score described more progressed state |
| Concentration of blood parameters and change to BL - IL2 | Day 4 | percentage of change of concentration of IL-2 |
| Assessment of intake of concomitant medication | Day 14 | Type and average daily dose of concomitant medication and total dose of paracetamol |
| Number of patients with hyposmia or anosmia | Day 4 | Number of patients with hyposmia or anosmia |
| proportion of patients with hyposmia or anosmia | Day 4 | proportion of patients with hyposmia or anosmia |
| Number of patients with fever | Day 4 | Number of patients with fever |
| proportion of patients with fever | Day 4 | proportion of patients with fever |
| Number of patients with COVID-19 vaccination | Day 4 | Number of patients with COVID-19 vaccination |
| proportions of patients with COVID-19 vaccination | Day 4 | proportions of patients with COVID-19 vaccination |
| Number of recovered COVID-19 patients | Day 4 | Number of recovered COVID-19 patients |
| proportion of recovered COVID-19 patients | Day 4 | proportion of recovered COVID-19 patients |
| Assessment of severe acute respiratory syndrome (SARS)- Corona virus (CoV) -2 negativity | Day 4 | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) |
| Assessment of SARS-CoV-2 negativity | Day 7 | Assessment of SARS-CoV-2 negativity measured by polymerase chain reaction (PCR) test) |
| Assessment of compliance | Day 4 | Compliance to investigational medicinal product (IMP) by dose taken and as documented in patient diary |
| Number of adverse events (AE) | through study completion, average 28 days | Number of adverse events (AE) |
| Number of serious adverse events (SAE) | through study completion, average 28 days | Number of serious adverse events (SAE) |
| Type and severity of adverse events | through study completion, average 28 days | Type and severity of adverse events |
| Type and severity of serious adverse events | through study completion, average 28 days | Type and severity of serious adverse events |
| Seriousness and relatedness of AEs | through study completion, average 28 days | Seriousness and relatedness of AEs |
| Seriousness and relatedness of SAEs | through study completion, average 28 days | Seriousness and relatedness of SAEs |
| Assessment of oxygen saturation | Day 4 | Oxygen saturation measured by finger clip and change to BL |
| Concentration of blood parameters and change to BL | Day 4 | absolute change of concentration of IL-2 |
| Concentration of blood parameters and change to BL (percentage): IL2 | Day 7 | percentage of change of concentration of IL-2 |
| Concentration of blood parameters and change to BL (absolute change): IL2 | Day 7 | absolute change of concentration of IL-2 |
| Concentration of blood parameters and change to BL (percentage) IL4 | Day 4 | percentage of change of concentration of IL-4 |
| Concentration of blood parameters and change to BL (absolute change): IL4 | Day 7 | absolute change of concentration of IL-4 |
| Concentration of blood parameters and change to BL (absolute change) IL4 | Day 14 | absolute change of concentration of IL-4 |
| Concentration of blood parameters and change to BL (absolute change) IL6 | Day 4 | absolute change of concentration of IL-6 |
| Concentration of blood parameters and change to BL (percentage) IL6 | Day 4 | percentage of change of concentration of IL-6 |
| Concentration of blood parameters and change to BL (percentage) IL8 | Day 4 | percentage of change of concentration of IL-8 |
| Concentration of blood parameters and change to BL (absolute change) IL8 | Day 4 | absolute change of concentration of IL-8 |
| Concentration of blood parameters and change to BL (percentage): | Day 7 | percentage of change of concentration of IL-8 |
| Concentration of blood parameters and change to BL (absolute change): | Day 7 | absolute change of concentration of IL-8 |
| Concentration of blood parameters and change to BL (absolute change IL8): | Day 14 | absolute change of concentration of IL-8 |
| Concentration of blood parameters and change to BL (absolute change IL10): | Day 4 | absolute change of concentration of IL-10 |
| Concentration of blood parameters and change to BL (IL10 percentage): | Day 4 | percentage of change of concentration of IL-10 |
Countries
Germany
Outcome results
None listed